DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production

Friederike Meyer-Wentrup, Alessandra Cambi, Ben J. Joosten, Maaike W. Looman, I. De Jolanda M Vries, Carl G. Figdor, Gosse J. Adema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

122 Citaten (Scopus)


C-type lectin receptors (CLRs) expressed on APCs play a pivotal role in the immune system as pattern-recognition and antigen-uptake receptors. In addition, they may signal directly, leading to cytokine production and immune modulation. To this end, some CLRs, like dectin-l and dendritic cell immunoreceptor (DCIR), contain in-tracellular ITIMs or ITAMs. In this study, we explored expression and function of the ITIM-con-taining CLR DCIR on professional APCs. DCIR is expressed on immature and mature monocyte-de-rived DCs (moDC) but also on monocytes, macro-phages, B cells, and freshly isolated myeloid and plasmacytoid DCs. We show that endogenous DCIR is internalized efficiently into human moDC after triggering with DCIR-specific mAb. DCIR in-ternalization is clathrin-dependent and leads to its localization in the endo-/lysosomal compartment, including lysosome-associated membrane pro- tein-1+ lysosomes. DCIR triggering affected neither TLR4- nor TLR8-mediated CD80 and CD86 up-regulation. Interestingly, it did inhibit TLR8-mediated IL-12 and TNF-α production significantly, and TLR2-, TLR3-, or TLR4-induced cy- tokine production was not affected. Collectively, the data presented characterize DCIR as an APC receptor that is endocytosed efficiently in a clathrin-dependent manner and negatively affects TLR8-mediated cytokine production. These data provide further support to the concept of CLR/ TLR cross-talk in modulating immune responses. copy; Society for Leukocyte Biology.

Originele taal-2Engels
Pagina's (van-tot)518-525
Aantal pagina's8
TijdschriftJournal of Leukocyte Biology
Nummer van het tijdschrift3
StatusGepubliceerd - 1 mrt. 2009
Extern gepubliceerdJa


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